Novel Therapies From The World Of Biotechnology

By now, most of us know someone who has benefited from the wide range of protein therapeutics produced by the biopharmaceutical industry; someone who had a heart attack or stroke and received t-PA (tissue plasminogen activator), someone with cancer who received Herceptin® or Avastin®, or perhaps someone with rheumatoid arthritis who received one of the many TNF inhibitors like Enbrel®, Humira®, or Remicade®.

As amazing as these revolutionary therapeutics are, a whole range of even more incredible, non-protein therapeutics have recently entered or will enter the market in the next decade. Many of these first-in-class therapies will address previously untreatable conditions or undruggable targets. These therapies include peptides, nucleic acids, carbohydrates, vaccines, and cell-based therapies.

In 2017, the US FDA approved two chimeric antigen receptor (CAR) T-cell therapies, the first therapies of this kind to enter the market, to treat two forms of cancer, pediatric lymphoblastic leukemia and diffuse large B-cell lymphoma in adults. CAR T-cells are one type of immunotherapy in which a patient’s own immune system is harnessed to fight cancer. In CAR T-cell therapy, a patient’s T-cells are removed from the body, modified to recognize an antigen on the surface of a cancer cell and reintroduced into the patient. CAR T-cells are part of a broader class of cancer immunotherapies that include immunogenic peptides, nucleic acid vaccines, oncolytic viruses, and dendritic cell therapies. In all cases, the objective is to convince the patient’s immune system to recognize and destroy the tumor.

Nucleic acid therapies as a group have made dramatic strides in the last several years, finally bringing to fruition 40 years of research and development, with promises of antisense oligonucleotides to inhibit aberrant biological processes and gene therapy to cure genetic defects. In 2016, two first-in-class antisense RNA drugs were approved, Sarepta Therapeutics’ Exondys 51® (eteplirsen) to treat Duchenne muscular dystrophy and Biogen/Ionis’sSpinraza® (nusinersen) to treat spinal muscular atrophy, both rare genetic disorders. Critical modifications to natural nucleic acids including changes to the phosphate backbone, the ribose sugar, and the nucleotides have improved stability, increased trafficking by reducing the net charge, and significantly increased the affinity of oligonucleotides for their targets, increasing the utility of these molecules.

Gene therapy remains the Holy Grail for treatment of genetic disorders. Conceptually, gene therapy is straightforward; deliver DNA or RNA to the appropriate tissue to replace the missing or defective protein with adequate persistence to have a therapeutic effect. But, as always, the devil is in the details. The greatest challenge is delivery, followed by cost-effective production.

Early gene therapy trials were hindered by the death of a patient in 1999 in response to high-dose adenovirus administration and the development of leukemias in X-linked severe combined immunodeficiency patients caused by insertional mutagenesis. The first approved gene therapy product was withdrawn from the market in 2017, as at ~$1 million/treatment, it was too expensive for insurers or national health services to cover.

However, a recent therapy, GlaxoSmithKline’sStrimvelis (now marketed by Orchard Therapeutics), approved in Europe in May 2016, for severe combined immunodeficiency due to adenosine deaminase deficiency, is expected to be commercially successful. While still expensive at $665,000 a treatment, it requires a one-time treatment where patients’ stem cells are transduced, ex vivo, with a gamma retrovirus containing the human adenosine deaminase gene, conferring full immune reconstitution. To date, all 18 patients in the clinical trials remain healthy, including one treated 17 years earlier.

In addition to treating and curing cancer, regenerative medicine, generally comprised of a differentiated or specialized cell type combined with some sort of scaffold, holds the other key to increasing our longevity and quality of life as our population ages. Four tissue products have been approved for regenerative medicine applications, LAVIV® (azficel-T), an autologous cellular product indicated for improvement of the appearance of moderate to severe nasolabial fold wrinkles in adults; Carticel® (autologous cultured chondrocytes) indicated for the repair of symptomatic cartilage defects of the femoral condyle (i.e., the knee); GINTUIT® (allogeneic cultured keratinocytes and fibroblasts in bovine collagen) indicated for the treatment of mucogingival conditions (i.e., gum disease) in adults, and MACI® (autologous cultured chondrocytes on porcine collagen membrane) for knee cartilage repair.

While the cardiovascular and neurodegenerative diseases that affect aging populations do not yet have tissue engineered solutions, they are certainly active areas for research and clinical studies.

About The Author

Susan T Sharfstein

Susan TSharfstein is a professor of nanobioscience at SUNY Polytechnic University. The primary focus of the research in the Sharfstein laboratory is on understanding the role of culture conditions and cell physiology on the use of living systems for industrially relevant processes.

Never miss a story

Sign up for Science Trend's Monthly Digest and stay up to date with new posts.

The welfare of farmed animals is under increasing scrutiny from consumers as well as governmental and industry bodies and plays an important part in the sustainability of farming for the future. Millions of dairy calves are born worldwide every year, […]

This study is the first prospective, population-based prevalence study particularly designed for idiopathic normal pressure hydrocephalus (iNPH). The finding of a 3.7% prevalence among individuals aged 65 years and older confirms that iNPH is a fairly common condition. This prevalence […]

Colorectal cancer is considered to be one of the most commonly diagnosed cancers and it also has one of the highest mortality rates among malignant tumors. The Molecular Oncology group at the IMDEA Food Institute (Madrid) is especially interested in […]

Modern Iraq is a relatively dry country faced with mounting water challenges. Ancient Southern Iraq, commonly referred to as Southern Mesopotamia, was also the home of some of the world’s first cities, which influenced many later societies through the development […]

The World Health Organization (WHO) calls antibiotic resistance “one of the biggest threats to global health, food security, and development today,” and the Centers for Disease Control and Prevention (CDC) calls it “one of the biggest public health challenges of […]

Science Trends connects scientists and their research with a global audience.

This website uses cookies. By continuing to use this website you are giving consent to cookies being used. Accept | Read More

Privacy & Cookies Policy

Privacy Overview

This website uses cookies to improve your experience while you navigate through the website. Out of these cookies, the cookies that are categorized as necessary are stored on your browser as they are as essential for the working of basic functionalities of the website. We also use third-party cookies that help us analyze and understand how you use this website. These cookies will be stored in your browser only with your consent. You also have the option to opt-out of these cookies. But opting out of some of these cookies may have an effect on your browsing experience.

This website uses cookies to improve your experience while you navigate through the website. Out of these cookies, the cookies that are categorized as necessary are stored on your browser as they are as essential for the working of basic functionalities of the website. We also use third-party cookies that help us analyze and understand how you use this website. These cookies will be stored in your browser only with your consent. You also have the option to opt-out of these cookies. But opting out of some of these cookies may have an effect on your browsing experience.

Necessary cookies are absolutely essential for the website to function properly. This category only includes cookies that ensures basic functionalities and security features of the website. These cookies do not store any personal information.